Contradicting earlier findings, a cohort study of adults hospitalised with moderate COVID-19, early aspirin use was associated with lower odds of 28-day in-hospital mortality, according to data from the US National Institutes of Health’s (NIH) National COVID Cohort Collaborative.
The findings contradict the UK RECOVERY trial, which found that all-cause mortality to be similar between aspirin and placebo groups, albeit with a small effect on discharge alive within 28 days in patients who received aspirin. More recently, the REMAP-CAP trial recently found antiplatelets to be unhelpful for COVID patients in the ICU.
In a large observational cohort study, early aspirin use was associated with lower in-hospital mortality rates by 28 days (10.2% vs 11.8% with no aspirin) with no significant increase in haemorrhagic complications such as GI or cerebral bleeding.
With early aspirin, pulmonary embolism was down, but not deep vein thrombosis, reported the ANCHOR group led by Dr Jonathan Chow of George Washington University School of Medicine and Health Sciences in Washington, DC. The authors said their study, published in JAMA Network Open, should leave the book open for aspirin in moderate COVID-19.
“Despite widespread vaccination efforts in wealthy countries, only 10% of the population in low-income countries is vaccinated. With low global vaccination rates and overwhelmed health systems, there continues to be a need for COVID-19 treatments, particularly in patients with moderate to severe disease,” the investigators wrote.
"A randomised clinical trial that includes diverse patients with moderate COVID-19 is warranted to adequately evaluate aspirin’s efficacy in patients with high-risk conditions,” according to them.
Chow and colleagues suggested that the mixed results of RECOVERY may be related to the study excluding people on antiplatelets prior to hospitalisation and the participants’ relatively low prevalence of comorbidities. In ANCHOR, those who appeared to benefit the most from early aspirin were patients over 60 and people with comorbidities, they reported.
“This is our third study and the culmination of 15 months of work looking at aspirin use in hospitalised COVID-19 patients. We continue to find that aspirin use is associated with improved outcomes and lower rates of death in hospitalised patients. What’s more, it’s cheap and readily available, which is important in parts of the world where more expensive therapeutics might not be as accessible,” Chow said.
The ANCHOR study was based on a data repository that pooled EHR files on COVID patients. Included were 112,269 people with moderate COVID-19 hospitalised across 64 health systems in the US, of whom 13.6% received aspirin on the first day of admission.
Notably, the trial data set came from the period from 1 January to 10 September 2020, well before the platform trials reported that therapeutic anticoagulation with heparin improved survival in hospitalised, non-critically ill COVID-19 patients.
In ANCHOR, 8.0% of the aspirin group and 1.2% of the no-aspirin group got therapeutic heparin by the first day of admission, which evened out to about 2.6% with inverse probability of treatment weighting.
By contrast, in RECOVERY, 34% of patients were on therapeutic-dose heparin and 60% were on standard prophylactic-dose heparin at randomisation. In the REMAP-CAP ICU trial, background anticoagulation was standard.
The RECOVERY authors had suggested that the anticoagulation provided adequate antithrombotic therapy that the antiplatelet didn’t improve on, writing: “The absence of meaningful benefit from aspirin in our trial could be because anti-platelet therapy confers no clinically significant additional benefit on top of high rates of anti-thrombotic therapy with LMWH [low molecular weight heparin] and corticosteroid treatment diminishing thrombo-inflammatory stimulation.”
Aspirin use in ANCHOR lasted a median five days and was more likely in people with chronic kidney disease, chronic obstructive pulmonary disease, heart disease, hypertension, and diabetes.
The overall cohort had a median age of 63, with 52.7% white patients, 16.1% black patients, and 3.8% Asian patients.
The retrospective study design left room for miscoding or underreporting of certain outcomes, the authors acknowledged.
Study details
Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19
Jonathan Chow, Ali Rahnavard, Mardi Gomberg-Maitland, Ranojoy Chatterjee, Pranay Patodi, David Yamane, Andrea Levine, Danielle Davison, Katrina Hawkins, Amanda Jackson, Megan Quintana, Allison Lankford, Ryan Keneally, Mustafa Al-Mashat, Daniel Fisher, Jeffrey Williams, Jeffrey Berger, Michael Mazzeffi, Keith Crandall.
Published in JAMA Network Open on 24 March 2022
Key Points
Question Is early aspirin use in hospitalised patients with moderate COVID-19 associated with lower odds of in-hospital mortality?
Findings In a cohort study of 112 269 patients with moderate COVID-19, early aspirin use during the first day of hospitalisation was associated with lower 28-day in-hospital mortality and pulmonary embolism incidence when compared with patients who did not receive early aspirin.
Meaning This study suggests that early aspirin use may be associated with lower odds of in-hospital mortality among hospitalised patients with moderate COVID-19; these findings warrant further study in a randomised clinical trial that includes diverse patients with cardiovascular comorbidities.
Abstract
Importance
Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalised patients with COVID-19, but aspirin’s efficacy in patients with moderate COVID-19 is not well studied.
Objective
To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19.
Design, Setting, and Participants
Observational cohort study of 112 269 hospitalised patients with moderate COVID-19, enrolled from January 1, 2020, to September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health’s National COVID Cohort Collaborative (N3C).
Exposure
Aspirin use within the first day of hospitalisation.
Main Outcome and Measures
The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.
Results
Among the 2 446 650 COVID-19–positive patients who were screened, 189 287 were hospitalised and 112 269 met study inclusion. For the full cohort, Median age was 63 years (IQR, 47-74 years); 16.1% of patients were African American, 3.8% were Asian, 52.7% were white, 5.0% were of other races and ethnicities, 22.4% were of unknown race and ethnicity. In-hospital mortality occurred in 10.9% of patients. After inverse probability treatment weighting, 28-day in-hospital mortality was significantly lower in those who received aspirin (10.2% vs 11.8%; odds ratio [OR], 0.85; 95% CI, 0.79-0.92; P < .001). The rate of pulmonary embolism, but not deep vein thrombosis, was also significantly lower in patients who received aspirin (1.0% vs 1.4%; OR, 0.71; 95% CI, 0.56-0.90; P = .004). Patients who received early aspirin did not have higher rates of gastrointestinal haemorrhage (0.8% aspirin vs 0.7% no aspirin; OR, 1.04; 95% CI, 0.82-1.33; P = .72), cerebral haemorrhage (0.6% aspirin vs 0.4% no aspirin; OR, 1.32; 95% CI, 0.92-1.88; P = .13), or blood transfusion (2.7% aspirin vs 2.3% no aspirin; OR, 1.14; 95% CI, 0.99-1.32; P = .06). The composite of haemorrhagic complications did not occur more often in those receiving aspirin (3.7% aspirin vs 3.2% no aspirin; OR, 1.13; 95% CI, 1.00-1.28; P = .054). Subgroups who appeared to benefit the most included patients older than 60 years (61-80 years: OR, 0.79; 95% CI, 0.72-0.87; P < .001; >80 years: OR, 0.79; 95% CI, 0.69-0.91; P < .001) and patients with comorbidities (1 comorbidity: 6.4% vs 9.2%; OR, 0.68; 95% CI, 0.55-0.83; P < .001; 2 comorbidities: 10.5% vs 12.8%; OR, 0.80; 95% CI, 0.69-0.93; P = .003; 3 comorbidities: 13.8% vs 17.0%, OR, 0.78; 95% CI, 0.68-0.89; P < .001; >3 comorbidities: 17.0% vs 21.6%; OR, 0.74; 95% CI, 0.66-0.84; P < .001).
Conclusions and Relevance
In this cohort study of US adults hospitalised with moderate COVID-19, early aspirin use was associated with lower odds of 28-day in-hospital mortality. A randomised clinical trial that includes diverse patients with moderate COVID-19 is warranted to adequately evaluate aspirin’s efficacy in patients with high-risk conditions.
See more from Medicalbrief archives:
Update on the RECOVERY trial – Aspirin added
REMAP-CAP trial: UK to roll out tocilizumab and sarilumab for ICU patients
Aspirin use for CVD may reduce risk of COVID-19 infection – Israeli study
Aspirin substantially lowers COVID risk — George Washington University study